Amyotrophic lateral sclerosis (ALS) is a severe disease causing motor neuron death, but a complete cure has not been developed and related genes have not been defined in more than 80% of cases. Here we compared whole genome sequencing results from a male ALS patient and his healthy parents to identify relevant variants, and chose one variant in the X-linked ATP7A gene, M1311V, as a strong disease-linked candidate after profound examination. Although this variant is not rare in the Ashkenazi Jewish population according to results in the genome aggregation database (gnomAD), CRISPR-mediated gene correction of this mutation in patient-derived and re-differentiated motor neurons drastically rescued neuronal activities and functions. These results suggest that the ATP7A M1311V mutation has a potential responsibility for ALS in this patient and might be a potential therapeutic target, revealed here by a personalized medicine strategy.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970999PMC
http://dx.doi.org/10.1038/s42003-020-0755-1DOI Listing

Publication Analysis

Top Keywords

crispr-mediated gene
8
gene correction
8
atp7a m1311v
8
amyotrophic lateral
8
lateral sclerosis
8
als patient
8
correction links
4
links atp7a
4
m1311v mutations
4
mutations amyotrophic
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!